Pharmacologic approaches to the treatment of obesity

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications & trials

Abstract

Obesity is a huge and increasing medical problem, with inadequate therapeutic options. One approach to the treatment of obesity is long-term pharmacotherapy. Drugs approved in the United States include orlistat, lorcaserin, phentermine/topiramate, buproprion/naltrexone, and liraglutide (high dose). The limited efficacy of single agents has led to the idea that additional agents and combination therapy are required. Progress in FY2020-21 includes the following: Mice are not simply small humans. Because mice are used widely to study diabetes and obesity, understanding their thermal biology is critical to translating observations from mice to humans. In humans, the heat needed to maintain body temperature is virtually all created as a byproduct of metabolic processes. People generally live in a thermoneutral zone, a 10C range of ambient temperatures over which core body temperature is maintained without increasing metabolic rate. In contrast, mice typically live below thermoneutrality. At room temperature (20-22C) about half of food intake is used to generate heat. Surprisingly, we found for mice no ambient temperature range over which energy expenditure and body temperature remained constant. Rather, we propose the concept of a thermoneutral point (TNP), a single ambient temperature, below which energy expenditure increases and above which body temperature increases. The mouse TNP was 29C in the resting/light phase and 33C in active/dark phase, a four-degree change every 12 hours. Thus, studying mice at thermoneutrality is not feasible. These results inform how mice can be used to model human obesity physiology and drug development.